Le mardi 11 février 2025, Madame Mona VEITHEN, titulaire d’un Master en sciences biomédicales à finalité approfondie et d'un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Madame Laurence DELACROIX et de Madame Brigitte MALGRANGE.

Cette épreuve consistera en la défense publique d'une thèse intitulée : «The importance of Proteostasis on the emergence and maintenance of neural diversity during mouse inner ear development». 

Le jury sera composé de :

Laurent NGUYEN (Président), Bernard PEERS (Secrétaire), Frédéric CLOTMAN (UCLouvain), Laurence DELACROIX, François LALLEMAND (Inst. Karolinska), Brigitte MALGRANGE, Francesca RAPINO.

Résumé de la thèse

Recently, scRNAseq studies have shown that the 3 otic neuronal subtypes (Ia, Ib, Ic) not only differ at the physiological and morphological level but also at the molecular level and are crucial for our ability to understand speech in a noisy background. Age-related hearing loss could already be linked to proteostasis disruption, but also environmental factors such as Noise exposure and ototoxic drugs can be linked to hearing loss caused by protein misfolding and aggregation. Here, we aimed to describe the role of proteostasis for neuronal diversity in the developing inner ear. In our mouse model we could show that the loss of ELP3, a known tRNA modifying enzyme and proteostasis regulator, during embryonic development impacts neuronal survival and correct subtype specification with a predominance of neurons that resemble Ia subtypes at the molecular level and Ic subtypes at the morphological level. These defects, appearing just before birth and leading to complete deafness, are not due to the proteostasis disruption but more likely due to the loss of a specific Elp3 target. In parallel, vestibular neurons do also show a diversity failure upon depletion of ELP3 with a spontaneous restoration of Calyx synapse-forming neurons without functional recuperation.